Food aromas are powerful appetitive cues that are intrinsic to foods'flavor and hedonic qualities, and such cues can facilitate overeating. Alcohol consumption similarly "primes" appetite, and contributes to overeating while under alcohol's acute effects. While neuroimaging of chemosensory brain networks is a major field of inquiry, testing how such sensory cues are differentially processed in lean and obese subjects has only recently begun. Further, there are no studies of how alcohol exposure alters the brain response to food odors, or how its disinhibiting qualities could facilitate overeating. Knowing the brain loci that respond to such appetitive stimuli, and how they are modified by body fat and alcohol exposure, will provide critical insights about the neural systems that underlie loss of control of eating. Our preliminary data suggest that when smelling food odors, obese subjects show a greater blood oxygen level-dependent (BOLD) response than lean subjects in the insula and hippocampus. Therefore, the main hypotheses of this proposal are that: A) Lean and obese subjects have different limbic responses to the olfactory cues that enhance motivation to eat, and B) Acute alcohol intoxication i) potentiates the brain's reward system response to food odors, and ii) affects brain systems involved in behavioral inhibition and eating restraint. To test these hypotheses, we have modified functional magnetic resonance imaging (fMRI) paradigms successfully used to study alcoholic drink aromas in subjects at risk for alcoholism and in ongoing work of inhibitory control under alcohol exposure. Our specific aims are to: 1) Determine the effect of adiposity on food aroma-induced responses of specific limbic-frontal (orbitofrontal cortex, medial frontal cortex, amygdala, hippocampus, and insula) areas, 2) Examine the relationships between caloric intake and food aroma-induced responses, and 3) Study the "apiritif" effect on the response to food odors. The studies in this proposal are particularly novel because, unlike prior neuroimaging research of obesity or food-cue responsiveness, we will relate the reward system response to food cues to real world conditions, including: 1) Subjects'eating behavior at realistic meal intervals that do not disrupt or interfere with circadian rhythms, 2) The effect of a meaningful reduction in calories on brain responses to food cues (as would be experienced under dieting conditions), and 3) The effect of alcohol as consumed before meals on the brain response to food cues, inhibition, and eating behavior. To accomplish these aims we will also use food aromas, which are particularly salient stimuli that convey a more immediate presence of reward than do food images. PUBLIC HEALTH RELEVANCE: Obesity is a significant public health problem associated with development of cardiovascular disease, diabetes and cancer. Studies in this application will use brain imaging techniques to: 1) clarify how food aromas activate reward systems in the brain to promote food intake, and differences in these responses between lean and obese women, 2) determine the brain pathways and behavioral mechanisms through which alcohol intoxication facilitates overeating.